5-fluorouracil Versus Placebo in Periocular Full Thickness Skin Grafts

NCT02705352 | Completed Phase 2 Results DMC

• 1 other identifier: 786680-1
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Full thickness skin grafts are an essential tool in surgery around the eyelids for reconstruction or rehabilitation following injury or surgery. Common conditions where skin grafts are needed include cicatricial ectropion, restoration of eyelid function after tumor removal, burns to the eyelids, or trauma. Early complications, occurring in the first 2 weeks after surgery, are rare: wound dehiscence, necrosis, infection, bleeding, partial or complete graft failure. However, late postoperative complications generally categorized as "scarring" (including graft hypertrophy and contraction, keloid formation, and hypo/hyper pigmentation) can limit the success and acceptability of the procedure by patients. Scars form following any insult to the deep dermis as a result of wound healing. Factors such as age, skin type, racial pigmentation, genetics, and sex may influence fibroblast proliferation as part of the healing response, resulting in a suboptimal result. Graft contraction is perhaps the most worrisome result, since it can result in failure of the initial surgery and may require additional surgery to correct. Many treatments have been used to manage these complications: corticosteroid injection, cryotherapy, pressure therapy, radiotherapy, laser therapy, silicone based products, and antimetabolite therapy. One such antimetabolite, 5-fluorouracil (5-FU), has been used over the last 15 years as an adjunct or primary treatment to modulate wound healing and scar formation. Other studies have demonstrated safety for cutaneous and subcutaneous injection in the periocular region. However, no controlled studies exist. This prospective, randomized, and double-blinded clinical study will evaluate the use and benefit of 5-FU versus saline in patients undergoing skin grafting for periocular reconstruction. The decision for the need for skin grafting will be at the discretion of the attending surgeon and will be made separate from enrollment in the study. Surgery will be performed as indicated. The study medication or placebo (normal saline) will be administered 2-3 weeks after surgery and then every 2-3 weeks afterwards for up to a total of 4 injections. After the injections, regular scheduled follow-up will be at 3, 6, and 12 months post-op. Outcomes at each study visit (up to 12 months post-operatively) include graft size, color, contour, and complications between study treatment group and placebo group.

Conditions

Ectropion; Skin Neoplasms

Keywords

Skin graft; 5-Fluorouracil; Periocular reconstruction

Outcome Measures

Primary Outcomes (1)

• Graft Size Change

  Full thickness skin grafts will be measured prior to treatment (at time of surgery) and 12 months after surgery. Although the graft will be measured at each visit, the outcome is the percent change from baseline at 12 months.

  12 months

Secondary Outcomes (3)

• Adverse Events

  12 months

• Early Post-operative Complications

  2 weeks after surgery

• Surgeon and Patient Satisfaction

  12 months

Study Arms (2)

5-Fluorouracil

EXPERIMENTAL

Antimetabolite will be injected 2 weeks after periocular reconstruction with full thickness skin graft. Injection will be repeated every 2 weeks for a total of up to 4 injections.

Drug: 5-Fluorouracil

Normal saline

PLACEBO COMPARATOR

Normal saline will be injected 2 weeks after periocular reconstruction with full thickness skin graft. Injection will be repeated every 2 weeks for a total of up to 4 injections.

Other: Normal saline

Interventions

5-Fluorouracil DRUG

Treatment medication

Also known as: 5-FU

5-Fluorouracil

Normal saline OTHER

Placebo

Also known as: Saline

Normal saline

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatients
• Ages 18 to 89 years of age
• Has a condition (e.g. trauma, skin/tissue defect, scar) requiring a skin graft for repair
• Sufficient education to understand study procedures and to give consent

You may not qualify if:

• Women lactating, pregnant or planning to get pregnant in the near future
• Immunosuppression/immunocompromise or serious/active infections
• Dihydropyrimidine dehydrogenase enzyme deficiency
• Severe hepatic or renal impairment or failure
• Unable to give consent or understand the study

Sponsors & Collaborators

• Massachusetts Eye and Ear Infirmary: lead

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Ectropion; Skin Neoplasms

Interventions

Fluorouracil; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Eyelid Diseases; Eye Diseases; Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Shyana Harper
• Organization: Massachusetts Eye and Ear

Shyana_harper@meei.harvard.edu

6173915982

Study Officials

• Michael K Yoon, MD

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ophthalmic Plastic and Reconstructive Surgery Attending

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 10, 2016
• Study Start: August 25, 2016
• Primary Completion: January 25, 2019
• Study Completion: January 25, 2019
• Last Updated: March 9, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)